Spermatogonial stem cells (SSCs) are adult stem cells in mammalian testes that maintain spermatogenesis and are essential for male fertility. Male infertility resulting from SSC loss after cancer treatments (e.g., chemotherapy and radiation) is a quality-of-life issue for many cancer survivors. In this proposal, we will test a nvel approach to preserving male fertility after cancer treatment that employs injections of the cytokine granulocyte colony-stimulating factor (G-CSF). In Aim 1, we will confirm that G-CSF administration prevents loss of spermatogenesis and fertility after chemotherapy and determine the optimal treatment regimen to maximize these beneficial effects. In Aim 2, we will determine whether G-CSF treatments act at the level of SSCs and will begin to address its protective mechanism of action. If found to be effective, G-CSF treatment would completely obviate the need for risky invasive interventions, and thus, has the potential to significantly improve the clinical paradigm for preserving male fertility after cancer treatment.